Research
Basic science: Obstetrics
Effects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia

https://doi.org/10.1016/j.ajog.2007.06.068Get rights and content

Objective

Our goal was to determine whether sildenafil increased fetal weight and favored fetal tolerance to induced asphyxia at birth in guinea pigs.

Study Design

Twenty guinea pigs were randomly allocated to placebo (n = 10) or sildenafil 50 μg/kg (n = 5) or 500 μg/kg (n = 5), starting from day 35 of gestation to delivery. Fetuses were delivered by cesarean section. Fetal asphyxia was induced by clamping the umbilical cord at birth for 5 minutes.

Results

Sildenafil protected the pups against induced asphyxia at birth in a dose-dependent manner (eg, partial pressure (tension) of carbon dioxide levels were 75.9 ± 19.3, 66.9 ± 18.8, and 54.8 ± 13.0 in the control and low- and high-dose sildenafil groups, respectively). The high-dose sildenafil group of piglets gained 1.5 times more body weight.

Conclusion

In guinea pigs, low doses of sildenafil administered from day 35 to the end of gestation favored fetal tolerability to induced intrapartum asphyxia. High doses of sildenafil increased fetal weight.

Section snippets

Animals

The study was approved and registered by the Committee of Animal Investigations (CINVA 220) at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF. During all the steps of the study, the animals were cared for according to the Mexican official norm NOM-062-ZOO-1999 Specifications Techniques of Reproduction, Care, and Use of Laboratory Animals.

Forty-three short-haired multiparous female, pigmented guinea pigs (Cavia porcellus) were housed for 5 days in a harem

Results

At 35 days of gestation, when pregnancy was confirmed and animals were randomly allocated to a treatment, the weight of the mothers was approximately 0.7 kg in all 3 study groups (P = .6) (Table 1). At term, the animals in the 3 study groups had increased their body weight by approximately 0.3 kg (P = .4). In contrast, the guinea piglets born to mothers treated with sildenafil 500 μg/kg were 1.5 times heavier and significantly larger than piglets born to either of the other 2 groups (Table 1).

Comment

Our study shows that, in guinea pigs, the offspring born to mothers treated with sildenafil have an increased survival rate to intrapartum asphyxia. Pulmonary arterial vasoconstriction occurs as a response to hypoxia, inducing a sustained elevation in the pulmonary blood pressures that causes pulmonary hypertension.10 The PDEs, mainly PDE5, are present in the pulmonary vascular smooth muscle,11 and PDE5 inhibitors including sildenafil have demonstrated to be effective in the pharmacological

Acknowledgments

The authors are grateful to Antonio Verduzco, DVM, for his help and training provided to investigators on the care and surgical procedures in the pregnant guinea pigs, and Ms Olivia Tischler for her valuable assistance in editing the manuscript. The study was not supported in any form by any pharmaceutical company.

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      In our study, the group without PPT presented pCO2 levels of approximately 112 mmHg at 0 min, which remained unchanged after the onset of the induced ischaemia. These data concur with those reported by Sánchez-Aparicio [6], who found a tendency towards an increase in pCO2 levels in guinea pig foetuses before, and at 5 min after, occlusion of the umbilical cord (75.9 ± 19.3 vs. 87 ± 22.9 mmHg, respectively). In our results, however, after 45 min of ischaemia, pCO2 levels decreased by 89% to approximately 22 mmHg.

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    Cite this article as: Sánchez-Aparicio P, Mota-Rojas D, Nava-Ocampo AA, et al. Effects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia. Am J Obstet Gynecol 2008;198:127.e1-127.e6.

    Reprints not available from the authors.

    The study was supported by grant UAM-PTC-028 from the Programa de Mejoramiento del Profesorado to the Cuerpo Académico de Etología, Producción Porcina y Fauna Silvestre, Universidad Autónoma Metropolitana, and the Sistema Nacional de Investigadores (to D.M.-R. M.E.T.-O., A.A.-R., E.A., and M.A.-S.). This study was part of the MSc thesis of P.S.-A., who was supported by grant 193059 from CONACYT at the Maestría en Ciencias de la Producción y de la Salud Animal, Universidad Nacional Autónoma de México.

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